Comprehensive Guide to Vitamins by Dr. James Meschino - HTML preview

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Vitamin E

Introduction

Vitamin E is the name given to a group of fat-soluble compounds, which include tocopherols and tocotrienols. The term “tocopherol” comes from the Greek word meaning “to bear offspring”. A Vitamin E deficiency in rats results in infertility and the re-introduction of Vitamin E to the diet corrects this problem. The most abundant and potent form of Vitamin E is d-alpha tocopherol (natural Vitamin E). Vitamin E is destroyed by light and oxygen. At the same time, however, it protects Vitamin A, Vitamin C and carotenes in food from oxidative destruction.

Absorption and Metabolism

As a fat-soluble nutrient, Vitamin E is absorbed from the intestinal tract via chylomicrons and lymph. It is carried in the blood by lipoproteins (i.e., VLDL and LDL) and is stored primarily in adipose tissue, with smaller amounts found in the liver, muscle tissue and adrenal glands.

Vitamin E is released into the circulation whenever fat is mobilized. Its metabolites are excreted both in urine and in feces.

Approximately 50 to 85 percent of Vitamin E is absorbed from the intestinal tract into the bloodstream, provided there is some fat present in the intestinal tract.

Recommended Daily Allowance (Vitamin E)

Equivalents

1 mg of d-alpha tocopherol (natural) = 1 alpha tocopheral equivalent (alpha T.E.) = 1.49 IU1

The “d” form denotes natural Vitamin E and is also known as RRR-alpha tocopherol.

The “dl” form denotes synthetic Vitamin E and is also known as all-race-alpha tocopherol.

Relative Biological Activity of Various Tocepherols2

N.B. In the human body, only the d-form is recognized (natural Vitamin E). Although the l-form has antioxidant activity, it may actually inhibit the d-form from entering cell membranes. Thus most authorities recommend supplementation using only natural Vitamin E (d-alpha-tocopherol).3,4,5 Recent studies suggest that natural Vitamin E is twice as bioactive as the synthetic form.6

Vitamin E Deficiency

Newborn infants have low tissue concentrations of Vitamin E because there is little transfer across the placenta. A haemolytic anemia can result in infants if their serum tocopherol levels are less than 0.5 mg/dl. A severe eye disorder called retrolental fibroplasia may also result.

This problem usually arises due to infant formulas high in polyunsaturated fats and containing iron. Because of formula changes, it is now rarely seen.

In adults Vitamin E deficiency can occur in:

Fat malabsorption syndromes, such as sprue, celiac disease, cystic fibrosis, and post-gastrectomy syndrome.

Sickle cell anemia and thalassemia.

Hemodialysis patients.

Symptoms of Vitamin E deficiency in adults include nerve damage, muscle weakness, poor coordination, involuntary movement of the eyes, red blood cell rupture leading to anemia (haemolytic anemia).

This suggests a neurological role for Vitamin E, in addition to its known antioxidant function.1,2,7

Functions

Antioxidant

As a fat-soluble antioxidant Vitamin E has been shown to protect various structures from oxidation and free radical damage, including:

a. LDL-cholesterol8

b. Cell Membrane structure9

c. Thymus gland10

d. White blood cells10

e. Lens and macula of the eye11,12

f. Nerve cells, including the brain13

Prostaglandin Synthesis

Vitamin E modulates prostanoid or eicosanoids biosynthesis. Prostanoids are compounds derived from

polyunsaturated fatty acids and include thromboxanes, prostacyclins, leukotrienes and three series of primary prostaglandins.1 By down regulating the conversion of arachidonic acid to the pro-inflammatory prostaglandin series 2, Vitamin E supplementation has been shown to reduce inflammatory conditions and also to decrease platelet clotting, although this effect may also be attributable to Vitamin E’s ability to directly antagonize the clotting function of Vitamin K.1,14,15

Nervous system function

As Vitamin E deficiency results in nerve damage, Vitamin E is required to preserve the normal function of nerve cells.6

Male Fertility

Vitamin E deficiency or marginal deficiency can result in decreased male fertility, which can be reversed via Vitamin E

supplementation.16

Supplementation Studies and Clinical Applications

Cardiovascular Disease

Substantial evidence suggests that Vitamin E supplementation can reduce the risk of coronary heart attack, stroke, angina, peripheral vascular disease and advancing atherosclerosis. The mechanisms of protection appears to be the following:

Decreased LDL-cholesterol oxidation: decreases oxidation of LDL cholesterol and thereby, reduces its uptake by macrophages and their subsequent transformation into foam cells. Foam cells are part of the atherosclerotic plaque and represent the primary mechanism by which cholesterol becomes incorporated into the atherosclerotic process, which narrows arteries throughout the body.8,17,18

Inhibition of Excessive Platelet Aggregation: via its effects on prostaglandin synthesis, Vitamin E appears to reduce the synthesis of thromboxanes A2, which increases platelet coaguability and it has been shown to antagonize the action of Vitamin K, which is a procoagulant. Thus, Vitamin E acts like a natural blood thinner, but with far less potency than aspirin or warfarin (coumadin).1,15,19

Inhibits the Proliferation of smooth muscle to grow into the lumen of the artery: as part of the atherosclerotic process platelets release a growth factor which normally encourages smooth muscle and connective tissue to proliferate and grow into the lumen of the artery, further reducing blood flow and narrowing arteries. Vitamin E has been shown to inhibit smooth muscle proliferation in experimental studies.20,21

Heart Disease Studies: a number of large prospective studies have demonstrated that Vitamin E supplementation of 100 I.U. or more is associated with approximately a 40 percent reduction in risk of heart disease compared to subjects not taking Vitamin E supplements or supplementing at a dosage below 100 I.U. per day.22,23,24

Intervention trials with high risk heart disease patients have also revealed that the use of Vitamin E supplementation of 100 IU or more per day, significantly reduced risk of heart disease, heart attack and fatal myocardial infarction. In the Cholesterol Lowering Atherosclerosis Study of 156 men (age 40-59) post bypass surgery, 100 IU or more of Vitamin E per day significantly decreased restenosis of coronary arteries, as evidenced by angiography studies after several years of follow-up.25

In the Cambridge Heart Antioxidant Study (CHAOS) supplementation with 400 or 800 I.U. of Vitamin E reduced risk of non-fatal heart attacks by 75 percent in high-risk patients as compared to those given the placebo. The beneficial effects were apparent after one year.26 The Finnish Alpha-Tocopheral, Beta-Carotene Cancer Prevention Study (ATBC) also showed a reduction in heart disease in subjects taking Vitamin E supplements compared to the placebo group.27 However, Vitamin E supplementation showed no benefit in the Heart Outcomes Prevention Evaluation Study.28

Angina: in the ATBC study mentioned above, Vitamin E supplement users also demonstrated a reduction in angina.27 Other studies have shown that Vitamin E has been effective in patients with existing angina pectoris.20,29 Intermittent Claudication: intermittent claudication has also been improved with Vitamin E supplementation.20,30-33

Alzheimer’s Disease

Emerging evidence links free radical damage to brain cells with the development and progression of dementia and Alzheimer’s disease. In the Alzheimer’s Disease Cooperative Study a daily dosage of 2,000 I.U. of Vitamin E slowed the functional deterioration of Alzheimer’s patients. Vitamin E appears to protect nerve cells from A beta-amyloid protein-induced oxidative damage and neurotoxicity.13,34,35

Prostate Cancer Prevention

Subjects in the ATBC study (mentioned above) taking 50 mg of Vitamin E (75 I.U.) showed a 32 percent decrease in the incidence of prostate cancer and a 41 percent decrease in prostate cancer death, compared to those taking the placebo.36

Post Cancer Treatment

In the study by Lockwood a cocktail of antioxidant supplements (including Vitamin E-2,500 I.U.) and other nutrients reduced the progression of breast cancer in women with existing axillary lymph node involvement.37

Primary Cancer Prevention

Results from the US National Institute on Aging study showed a 22 percent decrease in risk of cancer death compared to non-Vitamin E supplement users.38

Vitamin E exhibits a number of cancer prevention effects beyond antioxidant function, which include antiproliferative and apoptosis (programmed cell death) effects on certain human cancer cell lines as well as other protective functions.39-42

In the Iowa Women’s Health Study women with the highest intake of Vitamin E (primarily supplementation) had a 30 percent lower incidence of colon cancer compared to those demonstrating a low Vitamin E intake.43 Similar findings exist for cervical cancer (40 percent reduction in risk with high Vitamin E intake).44

The Iowa Women’s Health Study has more recently demonstrated that higher Vitamin E intake may also reduce risk of oral, pharyngeal, esophageal and gastric cancers.45 Vitamin E also blocks the formation of cancer causing nitrosamines in the human intestinal tract,68 in a similar fashion as Vitamin C.

Fibrocystic Breast Disease

Some studies have shown that 600 I.U. of Vitamin E taken as a supplement can reverse fibrocystic breast disease.46,47

Cataracts and Macular Degeneration

Several preliminary studies reveal that Vitamin E supplementation (usually in combination with other antioxidants) can reduce the risk of cataracts and halt or slow the progression of macular degeneration of the eye (some cases showed improved visual acuity) in intervention trials.48,49,50

Male Fertility

In one study infertile males (n=52) treated with 600-800 I.U. of Vitamin E demonstrated improvement in sperm quality; eleven were able to impregnate their spouses following Vitamin E treatment.51

Tardive Dyskinesia

Drugs that treat schizophrenia may trigger Tardive Dyskinesia due possibly to free radical damage to nerve cells. Vitamin E supplementation at 1,600 I.U. has been used successfully to treat Tardive Dyskinesia in these patients.52,53,54

HIV/AIDS

A nine year study involving 311 HIV-positive men showed that those patients with highest Vitamin E intakes had a 35 percent decrease in risk of progression to AIDS when compared to the lower intake group.55 Other studies suggest a similar protective effect.56,57

Hepatitis C

A 1997 preliminary study of 23 hepatitis C patients treated with 400 I.U. of Vitamin E, twice per day, revealed significant improvement in 11 of 23 patients as demonstrated by clinical testing of liver function.58

Asthma

A preliminary study has shown that supplementation with 400 I.U. of Vitamin E and 500 mg of Vitamin C increased peak flow capacity by 18 percent in a trial of 17 asthma sufferers (treadmill testing with peak flow lung function tests).59

Rheumatoid Arthritis and Osteoarthritis

Several studies have shown that Vitamin E supplementation at 400 I.U. per day or 895 IU, twice per day can reduce symptoms and signs of rheumatoid arthritis, when compared to placebo.14,60

Osteoarthritic patients have also shown benefit from Vitamin E supplementation.61,62

Diabetes

Vitamin E supplementation has been shown to improve insulin sensitivity (900 I.U. per day) in elderly subjects, as well as fasting glucose, triglycerides and LDL:HDL ratio.63 Vitamin E supplementation of 100 I.U. per day significantly lowered lipid peroxidation products and lipid levels in diabetic patients.64

Exercise-Induced Free Radical Damage

Studies are demonstrating that Vitamin E daily supplementation (400 I.U to 1,200 I.U.) reduces free radical damage induced by aerobic and strength training exercise, preserving muscle membrane structure and reducing muscle inflammation.65

Diabetes

Vitamin E studies with diabetic patients have generally revealed a number of significant benefits, which include:

Decreased LDL-Cholesterol oxidation

Improved insulin sensitivity

Lower triglycerides

Improved LDL:HDL ratio

Improved glucose tolerance

Lower fasting insulin levels.

In two trials, a daily dosage of 1,350 I.U. of Vitamin E was used for up to 4 months.66,67 However, in one trial a dosage as low as 100 I.U. per day of Vitamin E was shown to significantly lower lipid peroxidation and lipid levels over a three month period.64

Premenstrual Syndrome

Vitamin E supplementation (400 I.U.) has been shown to improve various symptoms in PMS. In one double-blind trial a success rate of 33 percent was realized with respect to physical symptoms, and 38 percent with anxiety.68,69

Parkinson’s Disease

Oxidative damage has been shown to be a contributing factor to Parkinson’s disease. A preliminary study demonstrated that Vitamin E supplementation significantly showed the progression of the disease. More recently, a double-blind study showed no benefit with Vitamin E supplementation. Further trials are underway.70,71

Restless Leg Syndrome

Vitamin E supplementation has been shown to be useful in some studies.72,73

For most conditions reviewed above, Vitamin E supplementation of 100-400 I.U. has been shown to provide the stated benefits. Higher doses have been used in the following cases:

Dosage Ranges

Adverse Side Effect and Toxicity

Vitamin E exhibits very little toxicity, even at high doses (i.e., 3,200 I.U. per day) in two-year trails.75 At doses higher than 800 I.U. per day, Vitamin E may increase the risk of a bleeding disorder. At higher doses it may infrequently cause high blood pressure, and abdominal pain.76

Increasing the dosage slowly over time may overcome the high blood pressure response that occurs in some patients (Author’s note). Begin at 100 I.U. per day.

Drug-Nutrient Interactions

Vitamin E supplementation can potentiate the anti-coagulant effect of aspirin, warfarin or coumadin at does above 400 I.U. In this case, a bleeding disorder may result. The general consensus is that Vitamin E at a daily dosage up to 400 I.U. can be taken concurrently with these medications.77,78

Drugs that deplete Vitamin E include:

Bile Acid Sequestrants

Gemfibrozil

Isoniazid

Mineral oil

Anticonvulsants (phenytoin, carbamazepine and Phenobarbital)

Orlistat - decreases Vitamin E absorption

Chitosan - decreases Vitamin E absorption if taken at the same time79-89

Vitamin E can serve a supportive interaction with the following drugs:

Allopurinol Cycolsporin Griseofulvin Simvastatin Sodium fluoride90

Neomycin impairs utilization of Vitamin E. Vitamin E can help reduce the side effects of the following drugs:

Amiodarone

Anthralin

Benzamycin

Chemotherapy

Cyclophosphamide

Dapsone

Haloperidol

Lindane

Risperidone76,90

High intakes of polyunsaturated fats can decrease Vitamin E levels in the body, thus increasing Vitamin E requirements.1

Pregnancy and Lactation

During pregnancy and lactation, the only supplements that are considered safe include standard prenatal vitamin and mineral supplements. All other supplements or dose alterations may pose a threat to the developing fetus and there is generally insufficient evidence at this time to determine an absolute level of safety for most dietary supplements other than a prenatal supplement. Any supplementation practices beyond a prenatal supplement should involve the cooperation of the attending physician (i.e., magnesium and the treatment of preeclampsia.)

References: Pregnancy and Lactation

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  3. The Healing Power of Herbs (2nd ed). Murray M. Prima Publishing 1995.
  4. Boon H. and Smith M. Health care professional training Program in complementary medicine. Institute of Applied Complementary Medicine Inc. 1997.

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- Shils M, Shike M, Olson J, Ross C. Modern Nutrition in Health and Disease. 9th ed. Baltimore, MD: Lippincott Williams & Wilkins; 1993.

- Escott-Stump S, Mahan LK, editors. Food, Nutrition and Diet Therapy. 10th ed. Philadelphia, PA: W.B. Saunders Company; 2000.

- Bowman B, Russell RM, editors. Present Knowledge in Nutrition, 8th ed. Washington, DC:.ILSI Press; 2001.

- Kreutler PA, Czajka-Narins DM, editors. Nutrition in Perspective. 2nd ed. Upper Saddle River, NJ: Prentice Hall Inc.; 1987.

Murray M. Encyclopaedia of Nutritional Supplements. California: Prima Publishing; 1996.

Horwitt MK. Vitamin E: a re-examination. Am J Clin Nutr 1976;29:569-78.

Ingold KU, et al. Biokinetics of and discriminating between dietary RRR- and SRRR-alpha-tocopherols in the male rat. Lipids 1978;22:163-172.

Burton GW, Traber MG. Vitamin E: antioxidant activity, biokinetics, and bioavailability. Annu Rev Nutr 1992;10:357-82.

Acuff RV, et al. Relative bioavailability of RRR- and all-rac-alpha-tocopheryl acetate in humans: studies using deuterated compounds. Am J Clin Nutr 1994;30:397-402.

Howeard L, et al. Reversible neurological symptoms caused by Vitamin E deficiency in a patient with short bowel syndrome. Am J Clin Nutr 1982;36:1243.

Princen HGM, et al. Supplementation with low doses of Vitamin E protects LDL from lipid peroxidation in men and women. Arterioscler Thromb Vasc Biol 1995;15:325-33.

Komiyama K, et al. Studies on the biological activity of tocotrienols. Chem Pharm Bull 1989;37:1369-81.

Meydani SN, et al. Vitamin E supplementation and in vivo immune response to healthy elderly subjects. A randomized controlled trial. JAMA 1997;277(17):1380-6.

Snodderly DM. Evidence for protection against age-related macular degeneration by corotenoids and antioxidant vitamins. Am J Clin Nutr 1995;62(Suppl):1448S-61S.

Bravetti G. Preventive medical treatment of senile cataract with Vitamin E and anthocyanosides: clinical evaluation. Ann Ophtalmol Clin Ocul 1989;115:109.

Sano M, et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzherimer’s disease. The Alzheimer’s Disease Cooperative Study. N Engl J Med 1997; 336(17)1216-22.

Scherak O, et al. High dosage Vitamin E therapy in patients with activated arthrosis. Z Rheumatol 1990;46(6):369-373.

McNeil JR. Interactions between herbal and conventional medicines. Can J Contin Med Educ 1999;11,12:97-113.

Vezina D, et al. Selenium-Vitamin E supplementation in infertile men. Effects on semen parameters and micronutrient levels and distribution. Biol Trace Elem Res 1996;53(Sum):1-3.

Abbey M, Nestel PH, Baghurst P. Antioxidant vitamins and low density lipoprotein oxidation. Am J Clin Nutr 1993;58:525-32.

Princen HMG, et al. Supplementation with Vitamin E, but not Beta-Carotene, in vivo effects low density lipoprotein from lipid peroxidation in vitro. Effect of cigarette smoking. Arterioscler Throm 1992;12:554-62.

FitzGerald GA, et al. Endeogenous prostacyclin and thromboxanes biosynthesis during chronic Vitamin E therapy in man. Ann N.Y. Acad Sci 1982;393:209.

Stamfer MJ, Rimm EB. Epidemiologic evidence for Vitamin E in prevention of cardiovascular disease. Am J Clin Nutr 1995;62(Suppl):1365S-9S.

Boscobolnik D, et al. Inhibition of cell proliferation by alpha-tocopherol: role of protein kinase C. J Biol Chem 1991 ;266:6188-94.

Stampfer MJ, et al. Vitamin E consumption and the risk of coronary disease in women. New Engl J Med 1993;328:1444-8.

Rimm EB. Vitamin E consumption and the risk of coronary heart disease in men. New Engl J Med 1993;328:1450-5.

Kushi LH, et al. Intake of Vitamin A, C, and E and postmenopausal breast cancer. The Iowa Women’s Health Study. Am J Epidemio 1996;144(2):163-74.

Virtamo J, et al. Vitamin E supplements are used in the treatment of the periopheral vascular disease, intermittent claudication. Arch Intern Med 1998;158(6):668-75.

Hodis HN, et al. Serial coronary angiographic evidence that antioxidant vitamin intake reduces progression of coronary artery atherosclerosis. JAMA 1995;273:1849-54.

Stephens NG, et al. Randomized controlled trial of Vitamin E in patients with coronary disease. Cambridge Heart Antioxidant Study (CHAOS). Lancet 1996;347:781-6.

Vitamin E supplementation and cardiovascular events in high-cost patients. Primary Care 2000;3(2):(Medscape) Gillilan RE, et al. Quantitative evaluation of Vitamin E in the treatment of angina pectoris. Am Heart J 1977;93:444.

Haegar K. Long term treatment of intermittent claudication with Vitamin E. Am J Clin Nutr 1974;27:1179.

Livingstone PD, et al. Treatment of intermittent claudication with Vitamin E. Lancet 1958;2:602.

Pinsky MJ. Treatment of intermittent claudication with alpha-tocopherol. J Am Pod Assoc 1980; 70:454.

Williams HTG, et al. Alpha-tocopherol in the treatment of intermittent claudication. Surg Gynec Obstet 1971 ;132:662.

Miller JW. Vitamin E and memory: is it vascular protection? Nutr Rev 2000;59(4):109-11.

Butterfield DA, et al. Vitamin E as an antioxidant/free radical scavenger against amyloid beta-peptide-induced oxidative stress in neocortical synaptosomal membranes and hippocampal neurons in culture: insight into Alzherimer’s Disease. Rev Neurosci 1999; 10(2): 141-9.

Heinonen OP, et al. Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: incidence and mortality in a controlled trial. J Natl Cancer Inst 1998;90(6):440-6.

Lockwood K, et alc “high risk” patients supplemented with nutritional antioxidants, essential fatty acids and coenzyme Q10. Mol Aspects Med 1994;15(Suppl):231S-40S.

Losonczy KG, et al. Vitamin E and Vitamin C supplement use and risk of all-cause and coronary heart disease mortality in older persons: the established populations for epidemiologic studies of the elderly. Am J Clin Nutr 1996;64(2):190-6.

Knekt P, et al. Vitamin E and cancer prevention. Am J Clin Nutr 1991; 53(Suppl):283-6.

Olson KB, et al. Vitamins A and E: further clues for prostate cancer prvention. J Natl Cancer Institi 1998;90(6)414-5.

Sigounas G, et al. DL-alpha tocopherol induces apoptosis in erythroleukemia, prostate and breast cancer cells. Nutr and Cancer 1997;28(1):30-5.

Prasad KN, et al. Effects of tocopherol (Vitamin E) acid succinate on morphological alterations and growth inhibition in melanoma cells in culture. Cancer Res 1982;42:550-5.

Bostick RM , et al. Reduced risk of colon cancer with high intake of Vitamin E: the Iowa Women’s Health Study. Cancer Res 1993; 53(18):423-7.

Palan PR, et al. Plasma levels of antioxidant Beta-Carotene and alpha-tocopherol in uterine cervix dysplasias and cancer. Nutr. Cancer 1991; 15(1): 13-20.

Zheng W, et al. Retinol, antioxidant vitamins, and cancers of the upper digestive tract in a prospective cohort study of post-menopausal women. Am J Epidemiol 1995;142(9):955-60.

London RS, et al. Endocrine parameters and alpha-tocopherol therapy of patients with mammary dysplasia. Cancer Res 1981 ;41:3811-3.

London RS, et al. The effect of alpha-tocopherol on premenstrual symptomatology: A double-blind study, II, Endocrine correlates. J Am Col Nutr 1984;3:351-6.

Robertson J, et al. A possible role for Vitamin C and E in cataract prevention. J Am J Clin Nutr 1991;53(Suppl1):346S-51S.

Richer S. Multicenter ophthalmic and nutritional age-related macular degeneration study. Part 1 and Part2. J Am Optom Assoc 1996;67:12-29 and 30-49, respectively.

Olson RJ. Supplemental antioxidant vitamins and minerals in patients with macular degeneration. J Am Coll Nutr

1991;10:550(Abstract52).

Suleiman SA, et al. Lipid peroxidation and human sperm mobility: Protective role of Vitamin E. J Androl 1996;17:530-7.

Schroeder DJ, Hart LL, Miyagi SL. Vitamin E in tardive dyskinesia. Annals Pharmacol 1993;27:311-2.

Egan MF, et al. Treatment of tardive dyskinesia with Vitamin E. Am J Psychiatry 1992;149:773-7.

Adler LA, et al. Vitamin E treatment of tardive dyskinesia. Am J Psychiatry 1993;150:1405-7.

Tang AM, et al. Association between serum Vitamin A and E levels and HIV-1 disease progression. AIDS 1997;5:613-20. Wang Y, et al. Potential therapeutics of Vitamin E in AIDS and HIV. Drugs 1997;48:327-38.

Liang B, et al. Vitamins and immunomodulation in AIDS. Nutr 1996;12:1-7.

Von Herbay A, et al. Vitamin E improves the aminotransferase status of patients suffering from viral hepatitis C: a randomized double- blind, placebo-controlled study. Free Radicol Res 1997;6:599-605.

The New Encyclopaedia of Vitamin, Supplements and Herbs. Reavley N: Evans M and Company, Inc.; 1998. p. 169.

Edmonds SE, et al. Putative analgenic activity of repeated oral dose of Vitamin E in the treatment of rheumatoid arthritis. Results of a prospective placebo-controlled, double-blind trial. 1997;56(11):649-55.

McAlindon TE, et al. Do antioxidant micronutrients protect against the development and progression of knee osteoarthritis? Athrit Rheum 1996;39:648-56.

Machtey I, et al. Tocopherol in osteoarthritis: a controlled pilot study. J Am Geriat Soc 1978;25(7):328-30.

Paolisso G, et al. Chronic intake of pharmacological doses of vitamin E might be useful in the therapy of elderly patients with coronary heart disease. Am J Clin Nutr 1995;61:848-52.

Jain SK, et al. The effect of modest Vitamin E supplementation on lipid peroxidation product and other cardiovascular risk factors in diabetic patients. Lipids 1996;31 (Suppl):87S-90S.

McBride JM, et al. Effect of resistance exercise on free radical production. Med Sci Sports Exerc 1998;30(1 ):67-72.

Corrigan JJ Jr., et al. Effect of Vitamin E on prothrombin levels in warfarin-induced vitamin K deficiency. Am J Clin Nutr 1981 ;39(4):1701-5.

West RJ, et al. The effect of cholestyramine on intestinal absorption. Gut 1975; 16(2):93-8.

Abraham GE. Nutritional factors in the etiology of the premenstrual tension syndromes. J Reprod Med 1983;28:446-64.

London RS, et al. The effect of alpha-tocopherol on premenstrual symptomatomlogy: a double-blind study. II. Endocrine Correlates. J Am Coll Nutr 1984;3:351-6.

Yoshikawa T. Free radicals and their scavengers in Parkinson’s disease. J of European Neurology 1993;33(Suppl 1):60S-8S.

Butterfield DA. Vitamin E and neurodegernerative disorders associated with oxidative stress. Nutri Neurosci 2002; 5(4): 229-39)

Ayres S Jr., et al. “Restless legs” syndrome: response to Vitamin E. J Appl Nutr 1973;25(8):8-15.

Ayres S,